Social stress increases susceptibility to develop substance use disorders, which can be modulated by intermittent exposure to a high-fat diet (HFD). However, both HFD and stress can elevate neuroinflammation levels under specific conditions. The objective of this study was to assess the protective role of intermittent exposure to HFD on the increase in ethanol consumption induced by social stress. The neuroinflammatory response in the hippocampus and the striatum was evaluated by quantitative real-time PCR of several gene expressions. Adult male OF1 mice were exposed to the repeated social defeat (RSD) protocol. After the last RSD, mice were classified into 3 groups according to different feeding conditions: standard diet; HFD for 1 hour two days a week; or 2 hours three days a week. The drinking in the dark paradigm was conducted three weeks after the last RSD to evaluate ethanol consumption. Results revealed that defeated animals fed on a standard diet consumed more ethanol than their non-stressed counterparts. However, stressed animals receiving HFD in both intermittent patterns exhibited lower ethanol consumption. Social stress increased expression of proinflammatory markers in the hippocampus (Il6, Tnfa, and Ucp2) and the striatum (Tnfa, Hmgb1, and Ucp2) of mice only when exposed to standard diet, suggesting that HFD exposition limits the neuroinflammatory state induced by social stress. To sum up, intermittent HFD administration prevents long-term increases in ethanol consumption induced by social stress and protects against the increased neuroinflammation in both the striatum and the hippocampus. Acknowledgments: PID-2020-112672RB-I00; (RIAPAd) RD21/0009/0005; (CIPROM/2021/080).